This renewal proposal describes plans to continue a vigorous chemistry-biology interface (CBI) predoctoral training program that is designed to train scientists in key aspects of fundamental organic and biological chemistry as well as in scientific disciplines at the interface of chemistry and biology. The program, now in its fourteenth year, further advances the interdisciplinary training of our most motivated and well-qualified students by focusing their graduate academic work around a core curriculum in areas spanning both chemical and biological disciplines. Each trainee may carry out his or her doctoral thesis research in one or more of the laboratories of the twenty-five faculty trainers affiliated with the following ten participating units: Chemistry and Chemical Biology, Plant Pathology, Molecular Biology and Genetics, Plant Biology, Biomedical Sciences, Chemical and Biomolecular Engineering, Microbiology and Immunology, Nutritional Sciences, The Boyce Thompson Institute for Plant Biology, and the Weill Institute for Cell and Molecular Biology. All participating faculty have strong research programs either in chemistry with strong biological connections or in biology with strong chemical connections and are well-funded. Their overall research interests are broadly distributed over chemistry (synthetic organic, bioorganic, biophysical, natural products, X-ray crystallography and proteomics) and biology (protein structure and function, enzymology, immunology, signal transduction, chemotaxis, cell biology, host/pathogen interactions and genetics). CBI trainees attend seminars in their core disciplines (usually weekly) in their respective units, participate together with faculty in a special monthly CBI seminar program, and organize monthly CBI "literature lunches". Two additional features distinguish the Cornell CBI program. First, trainees invite, organize, and host special CBI seminar speakers each semester. Secondly, trainees take internships in a laboratory distinct from that of their thesis research, usually in the context of a biotech, life science, or pharmaceutical company. Through this experience they gain exposure to, and experience in, interdisciplinary biomedical research. PUBLIC HEALTH RELEVANCE: The diagnosis and treatment of disease increasingly relies on a detailed molecular understanding of the underlying conditions and the ability to intervene with chemical precision. The Chemistry and Biology Interface training program at Cornell University unites a diverse group of chemists and biologists in an integrative graduate program that aims to produce future researchers that are capable of addressing the most pressing medical challenges at the molecular level.